Compounds of formula 
wherein R1 is hydrogen or a lower alkyl radical and n is 4, 5, or 6 are known in U.S. Pat. No. 4,024,175 and its divisional U.S. Pat. No. 4,087,544. The uses disclosed are: protective effect against cramp induced by thiosemicarbazide; protective action against cardiazole cramp; the cerebral diseases, epilepsy, faintness attacks, hypokinesia, and cranial traumas; and improvement in cerebral functions. The compounds are useful in geriatric patients. The patents are hereby incorporated by reference.
The instant invention is a series of novel bicyclic amino acids, their pharmaceutically acceptable salts, and the prodrugs of the amino acids.
The compounds are those of formula: 
wherein n is an integer of from 1 to 4, where there are stereocenters, each center may be independently R or S.
Preferred compounds of the invention are those of Formulae I-IV above wherein n is an integer of from 2 to 4.
Other preferred compounds are those of Formula I above.
Especially preferred compounds are:
(1xcex1,6xcex1,8xcex2)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid;
(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid;
(2-Aminomethyl-octahydro-pentalen-2-y)-acetic acid;
(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid;
(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid;
(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid; and
(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid.
Other preferred compounds are those selected from
(1xcex1,5xcex2)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
(1xcex1,5xcex2)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
(1xcex1,5xcex2)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
(1xcex1,6xcex2)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(1xcex1,7xcex2)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
(1xcex1,5xcex2)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
(1xcex1,5xcex2)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
(1xcex1,5xcex2)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
(1xcex1,6xcex2)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(1xcex1,7xcex2)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
(1xcex1,3xcex2,5xcex1)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
(1xcex1,3xcex1,5xcex1)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
(1xcex1,3xcex1,5xcex1)2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
(1xcex1,6xcex1,8xcex1)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(1xcex1,7xcex1,9xcex1)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
(1xcex1,3xcex2,5xcex1)(3-Aminomethyl-bicyclo[3.1.0]hex-3-yl)-acetic acid,
(1xcex1,3xcex2,5xcex1)(3-Aminomethyl-bicyclo[3.2.0]hept-3-yl)-acetic acid,
(1xcex1,3xcex2,5xcex1)(2-Aminomethyl-octahydro-pentalen-2-yl)-acetic acid,
(1xcex1,6xcex1,8xcex2)(2-Aminomethyl-octahydro-inden-2-yl)-acetic acid,
(1xcex1,7xcex1,9xcex2)(2-Aminomethyl-decahydro-azulen-2-yl)-acetic acid,
((1R,3R,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1R,3 S,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1S,3S,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1S,3R,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1R,3R,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1R,3 S,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1S,3S,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1S,3R,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((3xcex1R,5R,7xcex1S)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3xcex1R,5S,7xcex1S)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3xcex1S,5S,7xcex1R)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3xcex1S,5R,7xcex1R)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((2R,4xcex1S,8xcex1R)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2S,4xcex1S,8xcex1R)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2S,4xcex1R,8xcex1S)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2R,4xcex1S,8xcex1S)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2R,4xcex1S,9xcex1R)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((2S,4xcex1S,9xcex1R)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((2S,4xcex1R,9xcex1S)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((2R,4xcex1R,9xcex1S)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((1R,3R,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1R,3S,6S)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1S,3S,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1S,3R,6R)-3-Aminomethyl-bicyclo[4.1.0]hept-3-yl)-acetic acid,
((1R,3R,6R)3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1R,3S,6R)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1S,3S,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((1S,3R,6S)-3-Aminomethyl-bicyclo[4.2.0]oct-3-yl)-acetic acid,
((3xcex1R,5R,7xcex1R)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3xcex1R,5S,7xcex1R)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3xcex1S,5S,7xcex1S)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((3xcex1S,5R,7xcex1S)-5-Aminomethyl-octahydro-inden-5-yl)-acetic acid,
((2R,4xcex1R,8xcex1R)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2S,4xcex1S,8xcex1R)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2S,4xcex1R,8xcex1S)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2R,4xcex1S,8xcex1S)-2-Aminomethyl-decahydro-naphthalen-2-yl)-acetic acid,
((2R,4xcex1R,9xcex1R)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((2S,4xcex1R,9xcex1R)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid,
((2S,4xcex1S,9xcex1S)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid, and
((2R,4xcex1S,9xcex1S)-2-Aminomethyl-decahydro-benzocyclophepten-2-yl)-acetic acid.
The compounds of the invention are useful in treating a variety of disorders. The disorders include: epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, and sleep disorders.
Intermediates useful in the preparation of the final products are also included in the scope of the invention.